The Lancet has published the results of an analysis of two randomised controlled trial to review the effect size of the interaction between clopidogrel (Plavix®) and proton pump inhibitors (PPIs).

In the PRINCIPLE-TIMI 44 trial the primary outcome assessed inhibition of platelet aggregation at six hours by light-transmission aggregometry in 201 patients assigned to treatment with high dose clopidogrel or prasugrel. Inhibition of platelet aggregation was significantly lower for patients on a PPI and clopidogrel. The effect was not statistically significant for patients assigned to prasugrel.

In the TRITON-TIMI 38 trial the primary endpoint was the composite of cardiovascular death, myocardial infarction or stroke. 13,608 patients with an acute coronary syndrome were assigned to treatment with clopidogrel or prasugrel. 4,529 patients were on a PPI at randomisation. There was no association between PPI use and an increased risk of the primary endpoint for either study drug.

The authors of the study conclude that, "current findings do not support the need to avoid concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel or prasugrel". However, they also note limitations in their analysis. PPI usage was not randomised and residual confounding is possible despite multivariate adjustment. PPI usage data were collected at baseline and may have changed through the study and these analyses are both post-hoc.

Action: The Medicines and Healthcare products Regulatory Agency have advised clinicians have to avoid the combination of clopidogrel and PPI where possible. These data provide some reassurance that clinical efficacy may not be affected if the combination is unavoidable.